Understanding of the Recruitment of HDACs by MEF2, Based on Their Structure



=Understanding of the Recruitment of HDACs by MEF2, Based on Their Structure= A biological field that has recently gained status is the so called Epigenetics. This term refers to changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence. Among many factors that act as epigenetic regulators, we can find some proteins that deal with histone ornamentation, such as the antagonists histone acetyltranferases (HATs) and the histone deacetylases (HDACs). These proteins act repectively inserting/removing acetyl groups to lisine residues that are contained in histone proteins, making chromatin structures tighter/looser and as a result, promote/repress gene expression.

Among the subgroups of HDACs, we can cite the class IIa HDACs. Such proteins shuttle from nucleus to cytoplasm in a Ca++ dependent fashion and need to associate to other transcriptional factors, such as MEF2, to have their nuclear activity, because they are unable to anchor to the chromosomes by themselves.

Despite their significant physiological functions in muscle, immune and neuronal cells, the mechanism of recruitment of class II HDACs by MEF2 was not well understood until the publication of structure of the complex HDAC9/MEF2/DNA, in 2005 (1tqe).

Through the structure of this oligomer that was obtained by crystallography, we can see that HDAC9 is kept relatively far from the genomic DNA even after MEF2 binding to the chromosome. We can also easily observe a very well evolutionary conserved region near the DNA binding site of MEF2.

Additionally, by looking to the structure obtained by X-ray crystallography, one could also think that complexes HDAC9/MEF2/DNA dimerize in vivo. During the crystallization process, two complexes were contained in the same asymmetric unit, giving such a false impression. Thus, it is important to emphasize that the biological unit would be composed only by a monomer of HDAC9, a dimer of MEF2 and a fragment of double strand DNA.

Additional Resources
For Additional information, See Transcription and RNA Processing